ArticleAntioxidants & redox signaling2013
Direct sGC activation bypasses NO scavenging reactions of intravascular free oxy-hemoglobin and limits vasoconstriction.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Immobilized neuroglobin scavenges carbon monoxide from circulating carboxyhemoglobin.bioRxiv : the preprint server for biology · 2026Article
- Soluble guanylate cyclase stimulators and activators as potential antihypertensive drugs.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Review
- Twelve-hour normothermic liver perfusion in a rat model: characterization of the changes in the ex-situ bio-molecular phenotype and metabolism.Scientific reports · 2024Article
- Tandem P-selectin glycoprotein ligand immunoglobulin prevents lung vaso-occlusion in sickle cell disease mice.Experimental hematology · 2020Article
- Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their RegulationPhysiological reviews · 2019Review
- Nitric Oxide-Independent Soluble Guanylate Cyclase Activation Improves Vascular Function and Cardiac Remodeling in Sickle Cell Disease.American journal of respiratory cell and molecular biology · 2018Article
- Life-threatening perianaesthetic complications in five cats undergoing biliary tract surgery: case series and literature review.Journal of feline medicine and surgery · 2017Article
- Nitric oxide signalling and neuronal nitric oxide synthase in the heart under stress.F1000Research · 2017Review
- Strategies to increase nitric oxide signalling in cardiovascular disease.Nature reviews. Drug discovery · 2015Review
- Vasculopathy and pulmonary hypertension in sickle cell disease.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- Is nitrite the circulating endocrine effector of remote ischemic preconditioning?Circulation research · 2014Article
- New insights into the role of soluble guanylate cyclase in blood pressure regulation.Current opinion in nephrology and hypertension · 2014Review
- Hemolysis during cardiac surgery is associated with increased intravascular nitric oxide consumption and perioperative kidney and intestinal tissue damage.Frontiers in physiology · 2014Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
aimsHemoglobin-based oxygen carriers (HBOC) provide a potential alternative to red blood cell (RBC) transfusion. Their clinical application has been limited by adverse effects, in large part thought to be mediated by the intravascular scavenging of the vasodilator nitric oxide (NO) by cell-free plasma oxy-hemoglobin. Free hemoglobin may also cause endothelial dysfunction and platelet activation in hemolytic diseases and after transfusion of aged stored RBCs. The new soluble guanylate cyclase (sGC) stimulator Bay 41-8543 and sGC activator Bay 60-2770 directly modulate sGC, independent of NO bioavailability, providing a potential therapeutic mechanism to bypass hemoglobin-mediated NO inactivation.
resultsInfusions of human hemoglobin solutions and the HBOC Oxyglobin into rats produced a severe hypertensive response, even at low plasma heme concentrations approaching 10 μM. These reactions were only observed for ferrous oxy-hemoglobin and not analogs that do not rapidly scavenge NO. Infusions of L-NG-Nitroarginine methyl ester (L-NAME), a competitive NO synthase inhibitor, after hemoglobin infusion did not produce additive vasoconstriction, suggesting that vasoconstriction is related to scavenging of vascular NO. Open-chest hemodynamic studies confirmed that hypertension occurred secondary to direct effects on increasing vascular resistance, with limited negative cardiac inotropic effects. Intravascular hemoglobin reduced the vasodilatory potency of sodium nitroprusside (SNP) and sildenafil, but had no effect on vasodilatation by direct NO-independent activation of sGC by BAY 41-8543 and BAY 60-2770. INNOVATION AND
conclusionThese data suggest that both sGC stimulators and sGC activators could be used to restore cyclic guanosine monophosphate-dependent vasodilation in conditions where cell-free plasma hemoglobin is sufficient to inhibit endogenous NO signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.